An Independent Poor-Prognosis Subtype Synthesized Single-Sample mRNA Molecular Classification in Tumor Microenvironment of Bladder Cancer

Abstract

Background: Immunotherapy has become an essential suppressing tumor treatment with wide prospects, particular in advanced bladder cancer. However, the relationship between immune cell mixture and cancer cell phenotype is still unclear. Methods: To select specific immune genes forming subtype indicating disparate prognosis, we used BC transcriptomic profiles from six published datasets. Except for unsupervised clustering based on different expression of genes, we additionally performed binomial logistic regression, focusing on mRNA level of single sample. Results: Unsupervised clustering showed 4 clusters captured the best segmentation. After validation with survival data and simplification using binomial logistic regression, we found the poor prognosis cluster (cluster B&D) had specific immune related characteristics in tumor microenvironment. Bonding with clinical data, more proportion of risk factors were assigned into worse prognosis subtype. And immune cell infiltration, nucleotide polymorphism (SNP) and copy number variation (CNV) all showed difference between clusters. Through phenotypical analysis, we found metabolism and proliferation phenotypes associated with the immune clusters and mutually exclusive in BC, of which proliferation contributed to worse outcomes. Conclusion: With this novel clustering criterion based on immune related genes, we provide a better understanding of immune microenvironment, as the same time highlight a correlation between tumor phenotype and immune contexture. Funding Statement: This work was supported by the National key research and development program of China (Grant No. SQ2017YFC0908003), National Natural Science Foundation of China (Grant No.81702536, 81770756), the Sichuan Science and Technology Program (2017HH0063), China Postdoctoral Science Foundation (2017M612971), Post-Doctor Research Project, West China Hospital, Sichuan University (2018HXBH085), National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University (Z2018C01). Declaration of Interests: The authors have declared that no competing interest exists.